UNIT OF INHERITED CV DISEASES HEART CENTER...

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UNIT OF INHERITED CV DISEASES HEART CENTER FOR THE YOUNG AND ATHLETES A DPT OF CARDIOLOGY –UNIVERSITY OF ATHENS

ELECTRICAL STRUCTURAL

FUNCTIONAL

Bradycardia

Repolarisation anomalies

Voltage criteria for chamber enlargement

Arrhythmias

Increased chamber wall thickness and

cavity size

Enhanced diastolic filling

Augmentation of stroke volume

Maron, N Engl J Med, 2003

HCM vs ATHLETES

Differen'al*Diagnosis*Star'ng*Points*** **

 !!ECHO:!LVH!in!black!athletes!(13!–!16!mm)!

  ECG : Inverted T-waves   ARRHYTHMIAS   ARRHYTHMIAS

ATHLETE WITH LVH

HCM vs ATHLETES

Differen'al*Diagnosis*Star'ng*Points*

 *ECHO:*LVH*in*black*athletes*(13*–*16*mm)*  ECG : Inverted T-waves     ECG : Inverted T-waves

ARRHYTHMIAS   *ARRHYTHMIAS *

SUBCLINICAL FORM The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

Neal K. Lakdawala et al., Am J Cardiol 2011

Q waves and repolarization abnormalities are the most discriminating ECG features of sarcomere mutation carriers with and without LVH. However, owing to the limited sensitivity of ECG and echocardiographic screening, genetic testing is required to definitively identify at-risk family members.

Distinguishing ECG abnormalities in G/LVH subjects. (A–C) Q waves (black arrows) and repolarization changes (T-wave inversions [asterisks] and/or ST-segment depressions [arrowheads]) were significantly more common in G/LVH subjects than G normal control relatives. IVS interventricular septum thickness by echocardiography.

ATHLETES ECG

•  Cardiovascular remodelling in the conditioned athlete is frequently associated with physiologic ECG changes.

•  Abnormalities, however, may be detected which represent expression of an underlying heart disease which puts the athlete at risk of arrhythmic cardiac arrest during sport. EUROPEAN RECOMMENDATIONS Eur Heart J 2010

QTc

Distinct abnormalities (57 athletes – 12.4%)

LVH & repolarization abnormalities

V1-V2

V1-V3

460 elite athletes

LONG DISTANCE RUNNING INVERTED T WAVES V1-V4,

SOKOLOW,P-R:220

ELECTRICAL STRUCTURAL

FUNCTIONAL

Bradycardia

Repolarisation anomalies

Voltage criteria for chamber enlargement

Arrhythmias

Increased chamber wall thickness and

cavity size

Enhanced diastolic filling

Augmentation of stroke volume

ATLETES HEART OR PATHOLOGICAL SUBSTRATE

•  LVH ; 12-15 •  LVEDD DILATED •  RV DILATED •  Abnormal ECG •  Arrhythmias

13%

2% LVH Adult athletes

Male sex

Large BSA Endurance Sports

Black Ethnicity

Anabolic drugs

0

5

10

15

20

25

30

35

40

6 7 8 9 10 11 12 13 14 15 16

Maximal LVWT

% BlackWhite

13%

2%

Uniform/homogeneous LV wall thickness

Large/High normal LV Cavity (> 55)

LA diameter < 50

Absence of systolic anterior motion of the anterior mitral valve leaflet

Normal diastolic function

Echocardiographic Strain Imaging to Assess Early and Late Consequences of Sarcomere Mutations in Hypertrophic Cardiomyopathy Carolyn Y. Ho et al., Circ Cardiovasc Genet. 2009 Diastolic dysfunction is an early consequence of sarcomere mutations, whereas systolic dysfunction results from mutations combined with subsequent pathological remodeling. Identifying mechanistic pathways triggered by these mutations may begin to reshape the clinical paradigm for treatment, based on early diagnosis and disease prevention.

Representative 2D longitudinal strain (left) and strain rate (right) tracings from echocardiographic strain analysis in control, preclinical, and subjects with overt HCM. Measurements are taken from the interventricular septum. Tracings from the basal, mid, and apical segments are depicted in yellow, blue, and green, respectively. Arrows indicate peak values.

Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness Iris K Rüssel et al., J Cardiovasc Magn Reson 2011 Carriers with normal wall thickness display increased LV torsion and TECS-ratio with respect to controls, which might be due to subendocardial myocardial dysfunction.

Error bar plots of Peak LV Torsion (A) and TECS-ratio (B) (torsion to endocardial circumferential shortening) in the control and carrier group. The difference between both groups is significant.

- Isolated Sokolow-Lyon LVH +

+ Pathological Q waves -

+ Marked ST segment depression

+ Left bundle branch block -

+ Deep T wave inversions in any lead in Caucasian athletes -

+ Deep T wave inversions in inferior or lateral - leads in black athletes

HCM

Athlete’s Heart

Recommendations for interpretation of 12-lead electrocardiogram in the athlete

Domenico Corrado, Antonio Pelliccia, Hein Heidbuchel, Sanjay Sharma, Mark Link, Cristina Basso, Alessandro Biffi, Gianfranco Buja, Pietro Delise, Ihor Gussac, Aris Anastasakis, Mats Borjesson, Hans Halvor

Bjørnstad, François Carrè, Asterios Deligiannis, Dorian Dugmore, Robert Fagard, Jan Hoogsteen, Klaus P. Mellwig, Nicole Panhuyzen-Goedkoop, Erik Solberg Luc Vanhees, Jonathan Drezner, N.A. Mark Estes III Sabino

Iliceto, Barry J. Maron Roberto Peidro Peter J. Schwartz Ricardo Stein Gaetano Thiene, Paolo Zeppilli and William J. McKenna

The*document*provides*cardiologists*and*sports*medical*physicians*with*a*modern*approach*to*correct*interpreta'on*of*12Llead*ECG*in*the*athlete*and*emerging*understanding*of*incomplete*penetrance*of*inherited*cardiovascular*disease.*When*the*ECG*of*an*athlete*is*examined,*the*main*objec've*is*to*dis'nguish*between*physiological*paSerns*that*should*cause*no*alarm*and*those*that*require*ac'on*and/or*addi'onal*tes'ng*to*exclude*(or*confirm)*the*suspicion*of*an*underlying*cardiovascular*condi'on*carrying*the*risk*of*sudden*death*during*sports.*The*aim*of*the*present*posi'on*paper*is*to*provide*a*framework*for*this*dis'nc'on.*For*every*ECG*abnormality,*the*document*focuses*on*the*ensuing*clinical*workLup*required*for*differen'al*diagnosis*and*clinical*assessment.*When*appropriate*the*referral*op'ons*for*risk*stra'fica'on*and*cardiovascular*management*of*the*athlete*are*briefly*addressed.**********************************************************************************************************************Eur!Heart!J!!2010!

Inconclusive echo images (poor windows)

Unexplained ECG (deep T waves)

Visualises the antero-lateral wall

Diagnostic in apical HCM

Reveals myocardial fibrosis

CMR With Late Gadolinium Enhancement in Genotype Positive–Phenotype Negative Hypertrophic Cardiomyopathy Ethan J. Rowin et al., JACC, 2012 Ιn G+P- HCM patients, cardiac magnetic resonance (CMR) identified substantial late gadolinium enhancement (LGE) indicative of myocardial fibrosis (structural abnormality)

Cine and contrast-enhanced cardiac magnetic resonance (CMR) in a 44-year-old asymptomatic genotype-positive/phenotype-negative HCM woman with -tropomyosin mutation (TPM1 Asp175Asn), who underwent cardiovascular evaluation after the diagnosis of HCM in her 21 year-old son (Figure 2). (A) Cardiac magnetic resonance (CMR) end-diastolic short-axis and (B) 2-chamber views demonstrate normal left ventricle (LV) wall thicknesses (maximal wall dimension, 12 mm). (C to F) Contrast-enhanced CMR imaging views after intravenous injection of gadolinium showing extensive areas of late gadolinium enhancement (LGE), including involvement of the anterior (thin arrows) and posterior ventricular septum (thick arrows) on (C) apical and (D) mid-LV short axis images, anterior (thin arrows) and posterior (inferior) LV free wall (thick arrows) on (E) 2-chamber long-axis images and (F) posterior septum (arrows) on 4-chamber long-axis image; global ejection fraction and segmental LV wall motion were normal. LA left atrium; RA right atrium; RV right ventricle; VS ventricular septum.

HCM OR ATHLETE’S HEART?

Δηµοσιεύσεις

Metabolic

Parameters HCM

(n=27) Strength Athletes (n=19)

Endurance Athletes (n=20)

p-value

peakVO2% 77.7±12.2 73.9±6.7 136.4±11.5* <0.001

AT% 38.1±8.4 34.1±5.4 74.5±10.9* <0.001

pVO2(ml/kg/min) 33.4±6.8

31.5±2.7

58.1±4.6*

<0.001

AT (l/min) 1.2±0.3

1.1±0.2

2.5±0.4*

<0.001

O2P (ml/beat) 13.9±2.4 14.9±1.7 25.3±2.7* <0.001

ΔVO2/ΔWR (ml/min/W)

9.6±0.9 8.9±1.0 9.2±0.9 NS

VE/VCO2 slope 27.4±3.7 25.6±1.8 22.3±1.8* <0.001

Cardiopulmonary Exercise Testing Metabolic Parameters

Anastasakis A, Kotsiopoulou C, Rigopoulos A et al., Heart 2005; 91: 1477-8

CET Metabolic Parameter

Strength Athletes

peakVO2% 73.9±6.7

AT% 34.1±5.4

pVO2(ml/kg/min) 31.5±2.7

AT (l/min) 1.1±0.2

O2P (ml/beat) 14.9±1.7

ΔVO2/ΔWR (ml/min/W)

8.9±1.0

VE/VCO2 slope 25.6±1.8

Findings that reassure athlete’s heart (Sharma S et al., JACC 2000; 36(3):864)

1.  Peak oxygen consumption (pVO2) > 45ml/

kg/min or > 10-20% above the predicted maximum value

2.   Anaerobic threshold (ΑΤ) > 55% of the predicted peakVO2

3.   Oxygen pulse (Ο2P) at peak exericse > 20 ml/beat

Anastasakis A, Kotsiopoulou C, Rigopoulos A et al., Heart 2005; 91: 1477-8

  CET is an established method for d i f ferent ia l d iagnosis between patients with HCM and endurance athletes.

  CET has severe limitations when assess ing strength athletes with athletic heart syndrome.

+ TYPE OF SPORT

STRENTH ATHLETES

Diagnosis is available (1-2 months)

False negatives

GENETIC INTERPRENTATION

COST APPROACHABLE

Differential Diagnosis on Hypertrophic Cardiomyopathy vs Athletic Heart Syndrome* * Athletes with abnormal ECG A.*Stage!A*   Clinical!examinaEon*

  History*  Family*history*  Physical*examina'on*  ECG*  ECHO!–!Doppler!–!TDI!  Blood!and!urine!tests*

B.*

Stage!B*   Holter!rhythm*  Cardiopulmonary!exercise!tesEng*  Exercise!ECHO*  Clinical!evaluaEon!of!the!family!(Stage!A!or!B?)*  Detraining?*

C.*

Stage!C*   Detraining?*

  Cardiac!MRI!–!LGE*  GeneEcs!

CASE A

•  ATHLETE SYNDROME OR SUBCLINICAL FORM

SUBCLINICAL CARDIOMYOPATHY OR ATHLETIC HEART SYNDROME

•  ATHLETE FOOT BALL •  Age 16 y old

•  asymptomatic •  o/e = unremarkable •  Medical history (-)

•  Family history (-)

MRI

Contrast echo

C/P EXERCISE TEST

ATHLETE

decoditioning

NO FAMILY HISTORY

OF SUDDEN DEATH OR HCM SO …CLINICAL EVALUATION OF THE FAMILY

Cor Angio : normal

Abn ECG

Abn ECG CHD – 48y

CHD 78y

IHD (+)

SD (-)

Athlete with abnormal ECG THE PUZZLE and the weight of evidence

•  ASYMPTOMATIC •  YOUNG •  NORMAL ECHO •  ABNORMAL ECG (+) •  NORMAL HOLTER •  NORMAL C/P EXERCISE TEST •  NO FAMILY HISTORY OF HCM / SCD •  CLINICAL FAMILY SCREENING (+) •  DECODITIONING (?)

SUSPECTED HCM

HCM

Abn ECG

Abn ECG

CHD – 48y

CHD

78y

IHD (+)

SD (-)

CASE B

BLACK ATHLETE

•  25 y old •  Asymptomatic •  Clinical examination unremarkable •  Abnormal ECG •  Medical history = ICD for a while??????????

Physiology Pathology

Pathological Q waves

ST segment depression

Deep T wave inversions V5-

V6

Deep T wave inversions in contiguous inferior leads

Inverted T

waves in V1-V4

Voltage LVH

ST segment elevation

C/P EXERCISE TEST

FURTHER EVALUATION

•  HOLTER rhythm 48 h =54 Ve”s •  C/P exercise test = No arrhythmias •  Normal BP response

BLACK ATHLETE WITH LVH THE PUZZLE and the weight of evidence

•  Asymptomatic •  Clinical exam :unremarkable •  ECG inverted Τ waves •  LVWmax :15mm •  Diastolic function borderline for athlete •  pVO2: 31,2 ml/kgr/min (75% predicted) •  Few ventricular ectopics (holter 24 h) •  Family history – NO SCD

HCM ?

E –MAIL… a never ending story

PEDIGREE

Aborted SD ICD

60Y

?

?

BLACK ATHLETE WITH LVH THE PUZZLE and the weight of evidence

•  ECG inverted Τ waves •  LVWmax :15mm •  Diastolic function borderline for athlete •  pVO2: 31,2 ml/kgr/min (75% predicted) •  Family history of aborted sudden cardiac death

(brother). •  Few ventricular ectopics (holter 24 h) •  RACE IS AN IMPORTANT FACTOR BUT REMAINS A PART OF THE PUZZLE

HCM

Asymptomatic Athlete with T-wave inversion Management pathways

Scenario!A*DefiniEve!diagnosis!of!cardiac!disease!aUer!detailed!cardiac!evaluaEon*

  Cessa'on*of*compe''ve*sports*  Gene'c*tes'ng*for*family*management*

Scenario!B*V!Normal!cardiac!evaluaEon*V!No!family!history!of!inherited!cardiovascular!disease!or/and!sudden!cardiac!death*

  Unrestricted*par'cipa'on*to*compe''ve*sports*  Offer*gene'c*tes'ng?*  Yearly*cardiac*evalua'on*  Cardiac*evalua'on*of*first*degree*rela'ves*

Scenario!C*V!Mild!cardiac!abnormaliEes!(inconclusive!diagnosis)*V!No!family!history!of!inherited!cardiovascular!disease*

  Unrestricted*par'cipa'on*to*compe''ve*sports*  Offer*gene'c*tes'ng?*  Yearly*cardiac*evalua'on*  Cardiac*evalua'on*(ECG,*Echo)**of*first*degree*

rela'ves*(>10yrs)*Scenario!D*V!Mild!cardiac!abnormaliEes!(inconclusive!diagnosis)*V!Family!history!of!inherited!cardiovascular!disease*

  Restricted*par'cipa'on*to*mild*or*moderate*compe''ve*sports*

  Offer*gene'c*tes'ng*  Yearly*cardiac*evalua'on*  Cardiac*evalua'on*(ECG,*Echo)**of*first*degree*

rela'ves*(>10yrs)*

Athletic Heart Syndrome vs Hypertrophic Cardiomyopathy: Major – Minor criteria

Demographics* MAJOR! MINOR!

• **Family*History*of*Hypertrophic*Cardiomyopathy*(FHCM)*

• *Symptoms*

• *Female*gender* • *Family*History*of*Sudden*Cardiac*Death*(FHSCD)*• *Systolic*murmur*

ECG* MAJOR! MINOR!

• *Abnormal*Q*waves*in*at*least*2*leads*from*II,*III,*AvF*(in*absence*of*lec*anterior*hemiLblock)*or*V1LV4*or*I,*AvL,*V5,*V6*• *GNT*• *Nega've*T*waves**II,*III,*AVf,*V4*L*V6*or*I,*AvL,*V4LV6*

• *Nega've*T*waves*V1*–*V3*• *Deep*S*wave*V2*(>25mm)*• *Complete*BBB*or*interventricular*conduc'on*defect*in*LV*leads*

Structural!CharacterisEcs*

MAJOR! MINOR!

• *ASH*• *Complete*SAM*• *LVOT*gradient*>*50mmHg*• *LVEDD*<*45mm*• *LVH*>*13mm*in*the*anterior*septum*or*posterior*wall*• *LVH*>*15mm*in*the*posterior*septum*or*free*wall*

•  LVH*of*12mm*in*the*anterior*septum*or*posterior*wall*•  Incomplete*SAM*•  ****LVOT*gradient*<*50mmHg*•  LA*>*45mm*•  LVW*S/P*>*1,4*•  RVH*•  Cardiac*MRI*gadolinium:*LGE*(+)*

Athletic Heart Syndrome vs Hypertrophic Cardiomyopathy: Major – Minor criteria

Diagnosis or Strong Suspicion: 2 major

1 major – 2 minor 4 minor

FuncEonal!CharacterisEcs* MAJOR MINOR Diastolic!FuncEon!(<20yrs)*• *E<A*• *Eα*<*9*cm/sec*

Diastolic!FuncEon!(<20yrs)!• *Eα*<*13*cm/sec*• *Exercise*Echo:*LVOT*gradient*• *3D*Echo:*Torsion*• *2D*speckle*trecking:*diastolic*radial*strain*<*7cm/sec**

Lab* MAJOR MINOR • *Cardiopulmonary*Exercise*Tes'ng:*VO2max*>*50ml/kg/min,*or*>*120%*predicted*VO2max*(only*for*endurance*athletes)**• *Increased*BNP*

Others* MAJOR MINOR • *3*months*Detraining:*No*response*• *Gene'cs:*Posi've*sarcomere*muta'on*

MESSAGE A ATHLETIC REMODELLING – •  CAUCASIAN MEN •  BLACK RACE INVERTED T WAVES •  PART OF THE PROBLEM

IMAGING IS ESSENTIAL CURRENT APPROACH POLYPARAMETRIC

  Adequate information for the athlete comes from the CLINICAL EVALUATION OF THE FAMILY

  CET has severe limitations when assessing strength athletes with athletic heart syndrome.

  RACE is a part of the puzzle

  Distiquishing HCM from Athletic Heart is not just a story is an adventure

TYPE OF SPORT

MESSAGE B